Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range.

Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor

Sleep-related breathing disorders in patients with heart failure: current aspects of treatment. Part II

The second part of the review highlights treatments for different types of sleep apnea in patients with heart failure. In both obstructive and central sleep apnea, ventilatory support during sleep takes a special place in treatment. Therefore, the review details the role of different ventilation modes (in particular, CPAP therapy and adaptive servo-ventilation), analyzes available evidence-based medicine data. The role of low-flow oxygen therapy, surgical treatment, implantable devices, specific therapy (theophylline, acetazolamide) in the treatment of central sleep apnea is also shown, and a novel method of treating central sleep apnea is considered — phrenic nerve stimulation

Sleep-related breathing disorders in patients with heart failure with reduced and mildly reduced ejection fraction: main types and their dependence on heart failure etiology

Aim. To identify and study the nature of sleep-related breathing disorders (SBDs) in a cohort of hospitalized patients with heart failure (HF) with reduced and mildly reduced ejection fraction (EF), as well as to clarify the relationship between SBD type, etiology and severity of HF.Material and methods. The study included 117 patients with HF with reduced and mildly reduced ejection fraction hospitalized at the National Medical Research Center for Therapy and Preventive Medicine from 2019 to 2021. All patients underwent clinical and paraclinical examination, including cardiorespiratory sleep study. Patients were divided into three groups according to the type and severity of SBD: no or mild SBD, predominantly with obstructive sleep apnea (OSA) and predominantly with central sleep apnea (CSA). Severity of SBD and clinical data were compared between these groups.Results. A total of 5 patients (4,27%) did not have any SBDs, while 47 (40,17%) were diagnosed with CSA, and 65 (55,56%) — OSA of varying severity. The proportions of patients with moderate and severe CSA and OSA differed insignificantly and amounted to 35,9% (n=42) and 44,4% (n=52), respectively. There were following proportions of diseases related to HF: coronary artery disease (41,88%), nonischemic cardiomyopathy (26,5%), arrhythmogenic cardiomyopathy (15,38%) and other causes (16,24%) (hypertension, myocarditis, heart defects). We found that reduced EF <40%, end-diastolic volume >210 ml, and ventricular ectopy (>300 extrasystoles/day) were associated with CSA, and body mass index >30 kg/m2 was traditionally associated with OSA.Conclusion. More than half of HF patients with reduced and mildly reduced EF have SBDs. Decreased LVEF and ventricular ectopic activity are associated with CSA, while increased body mass index is associated with OSA. Consideration of SBD risk factors may improve patient phenotyping for individualized therapy

Two-dimensional Anderson-Hubbard model in DMFT+Sigma approximation

Density of states, dynamic (optical) conductivity and phase diagram of paramagnetic two-dimensional Anderson-Hubbard model with strong correlations and disorder are analyzed within the generalized dynamical mean-field theory (DMFT+Sigma approximation). Strong correlations are accounted by DMFT, while disorder is taken into account via the appropriate generalization of the self-consistent theory of localization. We consider the two-dimensional system with the rectangular "bare" density of states (DOS). The DMFT effective single impurity problem is solved by numerical renormalization group (NRG). Phases of "correlated metal", Mott insulator and correlated Anderson insulator are identified from the evolution of density of states, optical conductivity and localization length, demonstrating both Mott-Hubbard and Anderson metal-insulator transitions in two-dimensional systems of the finite size, allowing us to construct the complete zero-temperature phase diagram of paramagnetic Anderson-Hubbard model. Localization length in our approximation is practically independent of the strength of Hubbard correlations. However, the divergence of localization length in finite size two-dimensional system at small disorder signifies the existence of an effective Anderson transition.Comment: 10 pages, 10 figures, improve phase diagra

Shortened PQ interval in the differential diagnosis of Anderson-Fabry disease: a case report

In this article, we present a case of a patient with a late diagnosis of Fabry disease caused by a pathogenic variant in the GLA gene (p.1287_1288dup), who repeatedly attempted interventional treatment of Wolff-Parkinson-White Syndrome due to characteristic electrocardiographic pattern of ventricular preexcitation and paroxysmal arrhythmias. The proposed pathognomonic signs of the disease will ensure timely diagnosis and the appointment of specific treatment

OUTPATIENT REGISTER OF CARDIOVASCULAR DISEASES IN THE RYAZAN REGION (RECVASA): PRINCIPAL TASKS, EXPERIENCE OF DEVELOPMENT AND FIRST RESULTS

Aim. To estimate risk factors and comorbidity structure, cardiovascular diseases outcomes, evaluate their diagnostics and treatment quality in real outpatient practice using a register of patients with arterial hypertension (HT), ischemic heart disease (IHD), chronic heart failure (CHF) and atrial fibrillation (AF) in the Ryazan Region – the territorial subject ofRussian Federation with high cardiovascular mortality rate.Material and methods. The total of 1000 HT, IHD, CHF, AF patients, applied for general practitioners or cardiologists of theRyazan outpatient clinics in March-May of 2012 were sequentially enrolled in the outpatient REgister of CardioVAscular diseases (RECVASA).Results. According to outpatient cards data HT, IHD, CHF and AF were diagnosed in 99.0%; 70.9%; 74.8% and 13.7% of the 1000 cases, respectively. 820 (82%) patients revealed a concomitant cardiovascular pathology (cardiac comorbidity), at that the most frequent was combination of HT with IHD and CHF (50.4%). Diabetes mellitus was diagnosed in 209 (20.9%) patients. 770 (77%) patients were assessed on their total cholesterol level; smoking status and family history of heart diseases were estimated in 28 (2.8%) and 49 (4.9%) patients, respectively. Exercise tolerance test (stress-test) was carried out in 2% of the patients (including 2.8% of the IHD patients), 24-hour blood pressure (BP) and ECG monitoring – in 0.7% and 5.5%, respectively; echocardiography and ultrasound of brachiocephalic arteries (BCA) – in 25.6% and 8.6%, respectively; coronary angiography – in 1.6% (which includes 2.3% of the IHD patients). The following drug groups were prescribed most frequently: antiplatelet agents – in 60.4% of the cases (584 patients received acetylsalicylic acid and 20 – clopidogrel), ACE inhibitors – in 62.9%, β-blockers – in 43.9% of the patients. Target BP level was achieved in 245 of 956 cases (25.6%). 50.6% of IHD patients and 51.1% of hypercholesterolemic patients received statins.Conclusion. The pilot stage of the RECVASA study revealed a high incidence rate of cardiac comorbidity (82%) in patients with hypertension, IHD, CHF and AF, insufficient estimation of cardiovascular risk factors, inadequate frequency of stress-tests, 24-hour BP and ECG monitoring, echocardiography, BCA sonography, coronary angiography use, as well as a scarce prescription of warfarin in AF and statins in hypercholesterolemic patients. Improvement of correspondence to national guidelines is the main reserve for enhancement of diagnostics and treatment quality in patients with HT, IHD, CHF, AF and hypercholesterolemia

The Cryo-EM Structure of a Complete 30S Translation Initiation Complex from Escherichia coli

Formation of the 30S initiation complex (30S IC) is an important checkpoint in regulation of gene expression. The selection of mRNA, correct start codon, and the initiator fMet-tRNAfMet requires the presence of three initiation factors (IF1, IF2, IF3) of which IF3 and IF1 control the fidelity of the process, while IF2 recruits fMet-tRNAfMet. Here we present a cryo-EM reconstruction of the complete 30S IC, containing mRNA, fMet-tRNAfMet, IF1, IF2, and IF3. In the 30S IC, IF2 contacts IF1, the 30S subunit shoulder, and the CCA end of fMet-tRNAfMet, which occupies a novel P/I position (P/I1). The N-terminal domain of IF3 contacts the tRNA, whereas the C-terminal domain is bound to the platform of the 30S subunit. Binding of initiation factors and fMet-tRNAfMet induces a rotation of the head relative to the body of the 30S subunit, which is likely to prevail through 50S subunit joining until GTP hydrolysis and dissociation of IF2 take place. The structure provides insights into the mechanism of mRNA selection during translation initiation

Production of {\pi}+ and K+ mesons in argon-nucleus interactions at 3.2 AGeV

First physics results of the BM@N experiment at the Nuclotron/NICA complex are presented on {\pi}+ and K+ meson production in interactions of an argon beam with fixed targets of C, Al, Cu, Sn and Pb at 3.2 AGeV. Transverse momentum distributions, rapidity spectra and multiplicities of {\pi}+ and K+ mesons are measured. The results are compared with predictions of theoretical models and with other measurements at lower energies.Comment: 29 pages, 20 figure

Эпидемиология и результаты терапии первой линии ВИЧ-ассоциированной лимфомы Ходжкина

Introduction. The risk of developing Hodgkin lymphoma (HL) with HIV infection is higher than in the general population, and the course of the disease itself is more aggressive. Currently, there is no unified approach to the treatment of HIV-related HL, and data on its epidemiology in the Russian Federation are limited.The objective was to study epidemiological characteristics, the used therapeutic tactics and the results of treatment for HIV-related HL.Methods and materials. The multicenter retrospective study included 46 patients with HIV- related HL treated in 9 centers of the Russian Federation. Descriptive statistics methods were used, the analysis of overall survival (OS) and progression-free survival (PFS) was performed using the Kaplan–Meier method.Results. HIV-related HL is more often represented by an advanced stage, B-symptoms, and extranodal lesions. The ABVD regimen was used as the first-line therapy in 60 % for HIV-related HL. The overall response to therapy was 81.6 %, and the 2-year OS and PFS were 85 % and 49 %, respectively. Factors that worsened OS were CD4+˂266 cells/mcL and general somatic status ECOG≥2. Введение. Вероятность развития лимфомы Ходжкина (ЛХ) на фоне ВИЧ-инфекции выше, чем в общей популяции, а течение заболевания имеет более агрессивный характер. В настоящий момент отсутствует единый подход к терапии ЛХ на фоне ВИЧ, а данные об ее эпидемиологии в Российской Федерации ограничены.Цель – изучить эпидемиологическую характеристику, применяемую терапевтическую тактику и результаты лечения лимфомы Ходжкина на фоне ВИЧ-инфекции.Методы и материалы. В многоцентровое ретроспективное исследование были включены 46 пациентов с диагнозом «ЛХ» на фоне ВИЧ, получавших лечение в девяти центрах Российской Федерации. Применяли методы описательной статистки, анализ общей выживаемости (ОВ) и беспрогрессивной выживаемости (БПВ) выполняли с использованием метода Каплана – Мейера.Результаты. ЛХ на фоне ВИЧ чаще представлена распространенной стадией, В-симптомами и экстранодальным поражением. В качестве терапии первой линии ЛХ на фоне ВИЧ в 60 % случаев использовалась схема ABVD. Общий ответ на терапию составил 81,6 %, а 2-летняя ОВ и БПВ составили 85 и 49 % соответственно. Факторами, снижающими ОВ, являлись уровень CD4+<266 кл/мкл и общесоматический статус ECOG≥2. Ключевые слова: лимфома Ходжкина, ВИЧ, CD4+, ECOG, многоцентровое исследование, терапия первой линии>˂ 266 кл/мкл и общесоматический статус ECOG≥2.